tbuckley/cabot-search huggingface dataset:
JAMA Cardiology
Authors: Patrick O'gara, Marc Sabatine, Clyde Boston, Ann Yancy, Michael Pencina, Carolina North, Robert Harrington, Adrian Hernandez, Mhs Durham, North Carolina, Ajay Kirtane, New York, Roxana Mehran, Pradeep Natarajan, Kristen Boston, Seattle Patton, Washington Udelson, Sadiya Khan, Gregg Fonarow, Los Angeles, Sharlene Day, Laine Thomas, Akhil Narang, Julia Getts, Eugene Braunwald, Judith Hochman, Donald Lloyd-Jones, Scm Chicago, Michael Parmacek, Daniel Simon, Sidney Smith, Chapel Hill, Carolina Douglas, E Vaughan, Myron Weisfeldt, Maryland Douglas, P Zipes, Paul Armstrong, Shinya Goto, Peter Liu, Renato Lopes, Carolina Prabhakaran, Hugh Watkins, Harvey White, Habib Yacoub, Frs London, Gregory Curfman, Annette Flanagin, Michael Berkwits, Brenda Gregoline, Tracy Frey, Iris Lo, Kevin Brown, Bernadette Hromin, Erin Keenan, Rebecca Langley, Kris Simmons, Connie Manno, Sara Billings, Doug Brandt, Timothy Gray, Peter Olson, Juliet Orellana, Paul Ruich, Kirby Snell, Judith Ahlers, Stephanie Beckmeyer, Dawn Bielawski, Jane Calayag, Jan Clavey, Mary Coerver-Connolly, Amy Eutsey, Paul Jaworski, Ruth Kaufman, Laura King, Martha Lentz, Jenny Mackay, Nellie Mcgrew, Charon Pierson, Lori Ryan, Thressa Smith, Divya Sreekumar, Donna Thordsen, Christine Tilles, Emma Underdown, Cara Wallace, Becki Weiss, Christina West, Caroline Woods, Erin Kato, Jacob Kendall-Taylor, Monica Mungle, Lenette Gardner-Gullens, Fanny Brown, Anna Bukowski, Lee Calibeo, Jordan Faber, Andrew Given, Tosca Hall, Kenneth Otani, Caroline Sietmann, Angelia Waltower, Jesse Mcquarters, Elena Guobyte, Daniel Morrow, Shelly Steff, Jennifer Zeis, Eman Aly, Reuben Rios, Mary Ferkaluk, Jonathan Laxamana, Sidra Bonner, Heather Hsu, Andrew Ibrahim, Karen Bucher, Andy Rekito, Nick Reback, Lohitha Kethu, Marla Erson, Joseph Thornton, Thomas Easley, Brian Shields, Karen Adams-Taylor, Paul Gee, Anna Frazier, Monica Smith, Julie Burton, Ronna Hewitt, Mary Sieck, Geneine Someren, Jamaal Vargas, Content Systems, Mike Bujewski, Nathan Mitre, Digital Production, Regina Brownlee, Amanda Camino, Brenda Chandler-Grayer, Emily Dunn, Amy Evers, Maleeka Holden, Teri Hutchison, Dan Knowles, Joshua Lampinen, Natalie Marsh, Patricia Panek, Marla Seidell, La Son, Diggs Sledge, Julian Graphics, Joe Amft, Jonathan Chala, Maria Duda, Fred Furtner, Carolyn Hall, Maria Kowalkowski, Joy Farrell, Maria Giannini, Sasha Grossman, Kate Lander, Judith Literskis, Teresa Omiotek, Michael Ryder, James Madara, Kirsten Bibbins-Domingo, Robert Bonow
Journal: JAMA Cardiology (2023)

science, and evidence-based health policy.Health equity, especially when supported by original science, is a leading editorial priority.
Preclinical optimization of a GPC2-targeting CAR T-cell therapy for neuroblastoma
Authors: Ming Sun, Yingying Cao, Reona Okada, Jeyshka M Reyes-González, Hannah G Stack, Haiying Qin, Nan Li, Charlie Seibert, Michael C Kelly, Eytan Ruppin, Mitchell Ho, Carol J Thiele, Rosa Nguyen
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Although most patients with newly diagnosed high-risk neuroblastoma (NB) achieve remission after initial therapy, more than 50% experience late relapses caused by minimal residual disease (MRD) and succumb to their cancer. Therapeutic strategies to target MRD may benefit these children. We developed a new chimeric antigen receptor (CAR) targeting glypican-2 (GPC2) and conducted iterative preclinical engineering of the CAR structure to maximize its anti-tumor efficacy before clinical translation. Methods We evaluated different GPC2-CAR constructs by measuring the CAR activity in vitro. NOD-SCID mice engrafted orthotopically with human NB cell lines or patient-derived xenografts and treated with human CAR T cells served as in vivo models. Mechanistic studies were performed using single-cell RNA-sequencing. Results Applying stringent in vitro assays and orthotopic in vivo NB models, we demonstrated that our single-chain variable fragment, CT3, integrated into a CAR vector with a CD28 hinge, CD28 transmembrane, and 4-1BB co-stimulatory domain (CT3.28H.BBζ) elicits the best preclinical anti-NB activity compared with other tested CAR constructs. This enhanced activity was associated with an enrichment of CD8 + effector T cells in the tumor-microenvironment and upregulation of several effector molecules such as GNLY , GZMB , ZNF683 , and HMGN2 . Finally, we also showed that the CT3.28H.BBζ CAR we developed was more potent than a recently clinically tested GD2-targeted CAR to control NB growth in vivo. Conclusion Given the robust preclinical activity of CT3.28H.BBζ, these results form a promising basis for further clinical testing in children with NB.
Intratumoral BO-112 in combination with radiotherapy synergizes to achieve CD8 T-cell-mediated local tumor control
Authors: Maria E Rodriguez-Ruiz, Irantzu Serrano-Mendioroz, Eneko Garate-Soraluze, Paloma Sánchez-Mateos, Celia Barrio-Alonso, Inmaculada Rodríguez López, Victor Diaz Pascual, Leire Arbea Moreno, Maite Alvarez, Miguel F Sanmamed, Jose Luis Perez-Gracia, Helena Escuin-Ordinas, Marisol Quintero, Ignacio Melero
Journal: Journal for ImmunoTherapy of Cancer (2023)

Radioimmunotherapy combines irradiation of tumor lesions with immunotherapy to achieve local and abscopal control of cancer. Most immunotherapy agents are given systemically, but strategies for delivering immunotherapy locally are under clinical scrutiny to maximize efficacy and avoid toxicity. Local immunotherapy, by injecting various pathogen-associated molecular patterns, has shown efficacy both preclinically and clinically. BO-112 is a viral mimetic based on nanoplexed double-stranded RNA (poly I:C) which exerts immune-mediated antitumor effects in mice and humans on intratumoral delivery. BO-112 and focal irradiation were used to make the proof-of-concept for local immunotherapy plus radiation therapy combinations.Murine transplantable tumor cell lines (TS/A, MC38 and B16-OVA) were used to show increased immunogenic features under irradiation, as well as in bilateral tumor models in which only one of the lesions was irradiated or/and injected with BO-112. Flow cytometry and multiplex tissue immunofluorescence were used to determine the effects on antitumor immunity. Depletions of immune cell populations and knockout mice for the IFNAR and BATF-3 genes were used to delineate the immune system requirements for efficacy.In cultures of TS/A breast cancer cells, the combination of irradiation and BO-112 showed more prominent features of immunogenic tumor cell death in terms of calreticulin exposure. Injection of BO-112 into the tumor lesion receiving radiation achieved excellent control of the treated tumor and modest delays in contralateral tumor progression. Local effects were associated with more prominent infiltrates of antitumor cytotoxic tumor lymphocytes (CTLs). Importantly, local irradiation plus BO-112 in one of the tumor lesions that enhanced the therapeutic effects of radiotherapy on distant irradiated lesions that were not injected with BO-112. Hence, this beneficial effect of local irradiation plus BO-112 on a tumor lesion enhanced the therapeutic response to radiotherapy on distant non-injected lesions.This study demonstrates that local BO-112 immunotherapy and focal irradiation may act in synergy to achieve local tumor control. Irradiation plus BO-112 in one of the tumor lesions enhanced the therapeutic effects on distant irradiated lesions that were not injected with BO-112, suggesting strategies to treat oligometastatic patients with lesions susceptible to radiotherapy and with at least one tumor accessible for repeated BO-112 intratumoral injections.
A dermatologic assessment of 101 mpox (monkeypox) cases from 13 countries during the 2022 outbreak: Skin lesion morphology, clinical course, and scarring
Authors: Sonya Prasad, Cristina Galvan Casas, Alexis G. Strahan, L. Claire Fuller, Klint Peebles, Andrea Carugno, Kieron S. Leslie, Joanna L. Harp, Teodora Pumnea, Devon E. McMahon, Misha Rosenbach, Janet E. Lubov, Geoffrey Chen, Lindy P. Fox, Allen McMillen, Henry W. Lim, Alexander J. Stratigos, Terrence A. Cronin, Mark D. Kaufmann, George J. Hruza, Lars E. French, Esther E. Freeman
Journal: Journal of the American Academy of Dermatology (2023)
Circulating DNA fragmentomics and cancer screening
Authors: A.R. Thierry
Journal: Cell Genomics (2023)

The high fragmentation of nuclear circulating DNA (cirDNA) relies on chromatin organization and protection or packaging within mononucleosomes, the smallest and the most stabilized structure in the bloodstream. The detection of differing size patterns, termed fragmentomics, exploits information about the nucleosomal packing of DNA. Fragmentomics not only implies size pattern characterization but also considers the positioning and occupancy of nucleosomes, which result in cirDNA fragments being protected and persisting in the circulation. Fragmentomics can determine tissue of origin and distinguish cancer-derived cirDNA. The screening power of fragmentomics has been considerably strengthened in the omics era, as shown in the ongoing development of sophisticated technologies assisted by machine learning. Fragmentomics can thus be regarded as a strategy for characterizing cancer within individuals and offers an alternative or a synergistic supplement to mutation searches, methylation, or nucleosome positioning. As such, it offers potential for improving diagnostics and cancer screening.
Remote visualization of large-scale genomic alignments for collaborative clinical research and diagnosis of rare diseases
Authors: Alberto Corvò, Leslie Matalonga, Dylan Spalding, Alexander Senf, Steven Laurie, Daniel Picó-Amador, Marcos Fernandez-Callejo, Ida Paramonov, Anna Foix Romero, Emilio Garcia-Rios, Jorge Izquierdo Ciges, Anand Mohan, Coline Thomas, Andres Felipe Silva Valencia, Csaba Halmagyi, Mallory Ann Freeberg, Ana Töpf, Rita Horvath, Gary Saunders, Ivo Gut, Thomas Keane, Davide Piscia, Sergi Beltran
Journal: Cell Genomics (2023)

The Solve-RD project objectives include solving undiagnosed rare diseases (RD) through collaborative research on shared genome-phenome datasets. The RD-Connect Genome-Phenome Analysis Platform (GPAP), for data collation and analysis, and the European Genome-Phenome Archive (EGA), for file storage, are two key components of the Solve-RD infrastructure. Clinical researchers can identify candidate genetic variants within the RD-Connect GPAP and, thanks to the developments presented here as part of joint ELIXIR activities, are able to remotely visualize the corresponding alignments stored at the EGA. The Global Alliance for Genomics and Health (GA4GH) htsget streaming application programming interface (API) is used to retrieve alignment slices, which are rendered by an integrated genome viewer (IGV) instance embedded in the GPAP. As a result, it is no longer necessary for over 11,000 datasets to download large alignment files to visualize them locally. This work highlights the advantages, from both the user and infrastructure perspectives, of implementing interoperability standards for establishing federated genomics data networks.
Palmitoylation couples insulin hypersecretion with β cell failure in diabetes
Authors: Guifang Dong, Sangeeta Adak, George Spyropoulos, Qiang Zhang, Chu Feng, Li Yin, Sarah L. Speck, Zeenat Shyr, Shuntaro Morikawa, Rie Asada Kitamura, Rahul S. Kathayat, Bryan C. Dickinson, Xue Wen Ng, David W. Piston, Fumihiko Urano, Maria S. Remedi, Xiaochao Wei, Clay F. Semenkovich
Journal: Cell Metabolism (2023)
Effect of 5 weeks of oral acetazolamide on patients with pulmonary vascular disease: A randomized, double-blind, cross-over trial
Authors: M. Lichtblau, S. Saxer, J. Müller, P. Appenzeller, C. Berlier, S.R. Schneider, L. Mayer, M. Furian, E.I. Schwarz, E.R. Swenson, K.E. Bloch, S. Ulrich
Journal: Pulmonology (2023)

The carbonic anhydrase inhibitor acetazolamide stimulates ventilation through metabolic acidosis mediated by renal bicarbonate excretion. In animal models, acetazolamide attenuates acute hypoxia-induced pulmonary hypertension (PH), but its efficacy in treating patients with PH due to pulmonary vascular disease (PVD) is unknown. 28 PVD patients (15 pulmonary arterial hypertension, 13 distal chronic thromboembolic PH), 13 women, mean±SD age 61.6±15.0 years stable on PVD medications, were randomised in a double-blind crossover protocol to 5 weeks acetazolamide (250mg b.i.d) or placebo separated by a ≥2 week washout period. Primary endpoint was the change in 6-minute walk distance (6MWD) at 5 weeks. Additional endpoints included safety, tolerability, WHO functional class, quality of life, arterial blood gases, and hemodynamics (by echocardiography). Acetazolamide had no effect on 6MWD compared to placebo (treatment effect: mean change [95%CI] -18 [-40 to 4]m, p=0.102) but increased arterial blood oxygenation through hyperventilation induced by metabolic acidosis. Other measures including pulmonary hemodynamics were unchanged. No severe adverse effects occurred, side effects that occurred significantly more frequently with acetazolamide vs. placebo were change in taste (22/0%), paraesthesia (37/4%) and mild dyspnea (26/4%). In patients with PVD, acetazolamide did not change 6MWD compared to placebo despite improved blood oxygenation. Some patients reported a tolerable increase in dyspnoea during acetazolamide treatment, related to hyperventilation, induced by the mild drug-induced metabolic acidosis. Our findings do not support the use of acetazolamide to improve exercise in patients with PVD at this dosing. NCT02755298
Fully automated closed-loop insulin delivery in adults with type 2 diabetes: an open-label, single-center, randomized crossover trial
Authors: Aideen B. Daly, Charlotte K. Boughton, Munachiso Nwokolo, Sara Hartnell, Malgorzata E. Wilinska, Alina Cezar, Mark L. Evans, Roman Hovorka
Journal: Nature Medicine (2023)

In adults with type 2 diabetes, the benefits of fully closed-loop insulin delivery, which does not require meal bolusing, are unclear. In an open-label, single-center, randomized crossover study, 26 adults with type 2 diabetes (7 women and 19 men; (mean ± s.d.) age, 59 ± 11 years; baseline glycated hemoglobin (HbA1c), 75 ± 15 mmol mol-1 (9.0% ± 1.4%)) underwent two 8-week periods to compare the CamAPS HX fully closed-loop app with standard insulin therapy and a masked glucose sensor (control) in random order, with a 2-week to 4-week washout between periods. The primary endpoint was proportion of time in target glucose range (3.9-10.0 mmol l-1). Analysis was by intention to treat. Thirty participants were recruited between 16 December 2020 and 24 November 2021, of whom 28 were randomized to two groups (14 to closed-loop therapy first and 14 to control therapy first). Proportion of time in target glucose range (mean ± s.d.) was 66.3% ± 14.9% with closed-loop therapy versus 32.3% ± 24.7% with control therapy (mean difference, 35.3 percentage points; 95% confidence interval (CI), 28.0-42.6 percentage points; P < 0.001). Time > 10.0 mmol l-1 was 33.2% ± 14.8% with closed-loop therapy versus 67.0% ± 25.2% with control therapy (mean difference, -35.2 percentage points; 95% CI, -42.8 to -27.5 percentage points; P < 0.001). Mean glucose was lower during the closed-loop therapy period than during the control therapy period (9.2 ± 1.2 mmol l-1 versus 12.6 ± 3.0 mmol l-1, respectively; mean difference, -3.6 mmol l-1; 95% CI, -4.6 to -2.5 mmol l-1; P < 0.001). HbA1c was lower following closed-loop therapy (57 ± 9 mmol mol-1 (7.3% ± 0.8%)) than following control therapy (72 ± 13 mmol mol-1 (8.7% ± 1.2%); mean difference, -15 mmol mol-1; 95% CI, -11 to -20 mmol l-1 (mean difference, -1.4%; 95% CI, -1.0 to -1.8%); P < 0.001). Time < 3.9 mmol l-1 was similar between treatments (a median of 0.44% (interquartile range, 0.19-0.81%) during the closed-loop therapy period versus a median of 0.08% (interquartile range, 0.00-1.05%) during the control therapy period; P = 0.43). No severe hypoglycemia events occurred in either period. One treatment-related serious adverse event occurred during the closed-loop therapy period. Fully closed-loop insulin delivery improved glucose control without increasing hypoglycemia compared with standard insulin therapy and may represent a safe and efficacious method to improve outcomes in adults with type 2 diabetes. This study is registered with ClinicalTrials.gov (NCT04701424).
Successful 4-Year Outcome Following Convergent Ablation for Longstanding Persistent Atrial Fibrillation in an Octogenarian – Novel Therapy for an Old Condition in The Very Elderly
Authors: Riyaz A. Kaba
Journal: Clinical Cardiology and Cardiovascular Interventions (2022)

The most common age range for atrial fibrillation (AF) prevalence over the coming decades will potentially be in those over 75 years old. However, despite widespread recognition of the strong association between AF burden and age, the elderly are under-represented within trials evaluating invasive rhythm control strategies. We report the outcomes of a gentleman in his late eighties that underwent Convergent hybrid ablation for highly symptomatic and longstanding persistent AF. Now four years later and into his nineties, he remains in sinus rhythm and enjoys good cardiac health without the need for anti-arrhythmic drugs or further intervention. To our knowledge, this case report is the oldest patient to have successfully undergone Convergent ablation with enduring sinus rhythm with long-term follow-up, despite significant risk factors for AF recurrence. As the overall population ages, the emergence of this minimally invasive multidisciplinary ablation technique for AF may offer to similar patients benefits over percutaneous ablation strategies alone.
Inorganic/organic combination: Inorganic particles/polymer composites for tissue engineering applications
Authors: Astha Sharma, Ganesh R. Kokil, Yan He, Baboucarr Lowe, Arwa Salam, Tariq A. Altalhi, Qingsong Ye, Tushar Kumeria
Journal: Bioactive Materials (2023)

Biomaterials have ushered the field of tissue engineering and regeneration into a new era with the development of advanced composites. Among these, the composites of inorganic materials with organic polymers present unique structural and biochemical properties equivalent to naturally occurring hybrid systems such as bones, and thus are highly desired. The last decade has witnessed a steady increase in research on such systems with the focus being on mimicking the peculiar properties of inorganic/organic combination composites in nature. In this review, we discuss the recent progress on the use of inorganic particle/polymer composites for tissue engineering and regenerative medicine. We have elaborated the advantages of inorganic particle/polymer composites over their organic particle-based composite counterparts. As the inorganic particles play a crucial role in defining the features and regenerative capacity of such composites, the review puts a special emphasis on the various types of inorganic particles used in inorganic particle/polymer composites. The inorganic particles that are covered in this review are categorised into two broad types (1) solid (e.g
Promoting racial equity in digital health: applying a cross-disciplinary equity framework
Authors: Marium M. Raza, Kaushik P. Venkatesh, Joseph C. Kvedar
Journal: npj Digital Medicine (2023)

Even as innovation occurs within digital medicine, challenges around equity and racial health disparities remain. Golden et al. evaluate structural racism in their recent paper focused on reproductive health. They recommend a framework to Remove, Repair, Restructure, and Remediate. We propose applying the framework to three areas within digital medicine: artificial intelligence (AI) applications, wearable devices, and telehealth. With this approach, we can continue to work towards an equitable future for digital medicine.
Effectiveness of gamified team competition as mHealth intervention for medical interns: a cluster micro-randomized trial
Authors: Jitao Wang, Yu Fang, Elena Frank, Maureen A. Walton, Margit Burmeister, Ambuj Tewari, Walter Dempsey, Timothy NeCamp, Srijan Sen, Zhenke Wu
Journal: npj Digital Medicine (2023)

Gamification, the application of gaming elements to increase enjoyment and engagement, has the potential to improve the effectiveness of digital health interventions, while the effectiveness of competition gamification components remains poorly understood on residency. To address this gap, we evaluate the effect of smartphone-based gamified team competition intervention on daily step count and sleep duration via a micro-randomized trial on medical interns. Our aim is to assess potential improvements in the factors (namely step count and sleep) that may help interns cope with stress and improve well-being. In 1779 interns, team competition intervention significantly increases the mean daily step count by 105.8 steps (SE 35.8, p = 0.03) relative to the no competition arm, while does not significantly affect the mean daily sleep minutes (p = 0.76). Moderator analyses indicate that the causal effects of competition on daily step count and sleep minutes decreased by 14.5 steps (SE 10.2, p = 0.16) and 1.9 minutes (SE 0.6, p = 0.003) for each additional week-in-study, respectively. Intra-institutional competition negatively moderates the causal effect of competition upon daily step count by -90.3 steps (SE 86.5, p = 0.30). Our results show that gamified team competition delivered via mobile app significantly increases daily physical activity which suggests that team competition can function as a mobile health intervention tool to increase short-term physical activity levels for medical interns. Future improvements in strategies of forming competition opponents and introducing occasional competition breaks may improve the overall effectiveness.
Drug-drug interactions of ritonavir-boosted SARS-CoV-2 protease inhibitors in solid organ transplant recipients: experience from the initial use of lopinavir-ritonavir
Authors: Ruben Gonzalez-García, Joan-Ramon Roma, María Rodríguez-García, Natalia Arranz, Juan Ambrosioni, Marta Bodro, Maria-Ángeles Castel, Federic Cofan, Gonzalo Crespo, Fritz Diekmann, Marta Farrero, Alejandro Forner, Ana LLigoña, Maria Ángeles Marcos, Asunción Moreno, Pablo Ruiz, Dolors Soy, Mercè Brunet, Jose M. Miró, Montse Tuset
Journal: Clinical Microbiology and Infection (2023)
COVID-19 vaccines and a perspective on Africa
Authors: Alberto Mantovani, Maria Rescigno, Guido Forni, Francesca Tognon, Giovanni Putoto, Jerry Ictho, Peter Lochoro
Journal: Trends in Immunology (2023)

Vaccines have dramatically changed the COVID-19 pandemic. Over 30 vaccines that were developed on four main platforms are currently being used globally, but a deep dissection of the immunological mechanisms by which they operate is limited to only a few of them. Here, we review the evidence describing specific aspects of the modes of action of COVID-19 vaccines; these include innate immunity, trained innate immunity, and mucosal responses. We also discuss the use of COVID-19 vaccines in the African continent which is ridden with inequality in its access to vaccines and vaccine-related immunological research. We argue that strengthening immunology research in Africa should inform on fundamental aspects of vaccination, including the relevance of genetics, trained innate immunity, and microbiome diversity.
Low-dose PTCy plus low-dose ATG as GVHD prophylaxis after UD-PBSCT for hematologic malignancies: a prospective, multicenter, randomized controlled trial
Authors: Yingling Zu, Ruirui Gui, Zhen Li, Juan Wang, Yanli Zhang, Fengkuan Yu, Huifang Zhao, Xinrong Zhan, Zhongliang Wang, Pengtao Xing, Xianjing Wang, Huili Wang, Yongping Song, Jian Zhou
Journal: Blood Cancer Journal (2023)